CAJ | 학술논문

目的评价BML-111对大鼠失血性休克复苏诱发急性肺损伤时NF-κB通路的影响.方法健康成年雄性SD大鼠32只,体重200 ～ 250 g,采用随机数字表法,将其分为4组(n=8):假手术组(S组)、失血性休克复苏组(HSR组)、BML-111组和BML-111+脂氧素A4受体拮抗剂BOC-2组(BOC-2组).通过放血制备失血性休克模型,休克维持30 min,然后回输放出的血液及2倍放血量的乳酸钠林格氏液进行复苏.BOC-2组在放血前腹腔注射BOC-2 50 μg/kg,BML-111组和BOC-2组在复苏开始时腹腔注射BML-111 1 mg/kg.复苏结束后2h处死大鼠,取肺组织,用于观察肺组织的病理学改变,采用比色法测定MPO活性,采用免疫组化法测定ICAM-1的表达,采用ELISA法测定TNF-α的含量,采用Western blot法测定NF-κB p65与IκB-α的蛋白表达.结果与S组比较,HSR组肺组织MPO活性、ICAM-1表达水平和TNF-α含量升高,NF-κB p65蛋白表达上调,IκB-α蛋白表达下调(P＜0.05);与HSR组比较,BML-111组肺组织MPO活性、ICAM-1表达水平和TNF-α含量降低,NF-κB p65蛋白表达下调,IκB-α蛋白表达上调(P＜0.05),病理学损伤减轻;与BML-111组比较,BOC-2组肺组织MPO活性、ICAM-1表达水平和TNF-α含量升高,NF-κB p65蛋白表达上调,IκB-α蛋白表达下调(P＜0.05),病理学损伤加重.结论 BML-111通过抑制NF-κB通路激活,抑制炎性反应,从而减轻大鼠失血性休克复苏诱发急性肺损伤.
목적 평개BML-111대대서실혈성휴극복소유발급성폐손상시NF-κB통로적영향.방법 건강성년웅성SD대서32지,체중200 ～ 250 g,채용수궤수자표법,장기분위4조(n=8):가수술조(S조)、실혈성휴극복소조(HSR조)、BML-111조화BML-111+지양소A4수체길항제BOC-2조(BOC-2조).통과방혈제비실혈성휴극모형,휴극유지30 min,연후회수방출적혈액급2배방혈량적유산납림격씨액진행복소.BOC-2조재방혈전복강주사BOC-2 50 μg/kg,BML-111조화BOC-2조재복소개시시복강주사BML-111 1 mg/kg.복소결속후2h처사대서,취폐조직,용우관찰폐조직적병이학개변,채용비색법측정MPO활성,채용면역조화법측정ICAM-1적표체,채용ELISA법측정TNF-α적함량,채용Western blot법측정NF-κB p65여IκB-α적단백표체.결과 여S조비교,HSR조폐조직MPO활성、ICAM-1표체수평화TNF-α함량승고,NF-κB p65단백표체상조,IκB-α단백표체하조(P＜0.05);여HSR조비교,BML-111조폐조직MPO활성、ICAM-1표체수평화TNF-α함량강저,NF-κB p65단백표체하조,IκB-α단백표체상조(P＜0.05),병이학손상감경;여BML-111조비교,BOC-2조폐조직MPO활성、ICAM-1표체수평화TNF-α함량승고,NF-κB p65단백표체상조,IκB-α단백표체하조(P＜0.05),병이학손상가중.결론 BML-111통과억제NF-κB통로격활,억제염성반응,종이감경대서실혈성휴극복소유발급성폐손상.
Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.